Apoptosis in MCF-7 breast cancer cells induced by S-alkenylmercaptocysteine (CySSR) species derived from Allium tissues in combination with sodium selenite

•S-Allylmercaptocysteines (CySSR) act synergistically with sodium selenite to mediate apoptosis in breast cancer cells.•The major CySSRs derived from onion and garlic are similarly potent, but act preferentially on different cellular targets.•The proposed mechanism is that cells import and reduce CySSR, then export thiols to reduce selenite to the cytotoxic H2Se.

S-Allylmercaptocysteine (CySSA) from garlic is known to exhibit anti-cancer effects. Apoptosis induction by CySSA was contrasted with S-1-propenylmercaptocysteine (CySSPe) (the major onion analog) in the presence of Na2SeO3 (Se) in breast cancer cells MCF-7. The dose of CySSA or CySSPe alone required to reduce viable cells by 50% was >400 μM, and this was reduced to 62 μM and 91 μM for CySSA + Se and CySSPe + Se, respectively, at molar ratios of 39:1. Synergism of the mixtures was confirmed by isobologram analysis and the treatments evoked enhanced thiol efflux from MCF-7 cells. Apoptosis was confirmed by Annexin-V and propidium iodide staining. Cell cycle arrest occurred at the G2/M and sub-G1 interphases. Both CySSR + Se mixtures reduced the levels of Akt. CySSPe + Se elevated GSK-3 protein levels, whereas CySSA + Se did not. CySSR + Se mixtures enhanced phospho-c-Jun levels, with CySSA + Se more potent than CySSPe + Se. Corresponding increases in phospho-p53, Bax and Bad levels were observed, indicating apoptosis occurred via the mitochondrial pathway. Lack of caspases 6/7 activation implicated a caspase-independent pathway for apoptosis. Reduction of imported CySSR and export of thiols by MCF-7 cells facilitates the reduction of selenite to yield H2Se, a cytotoxic agent. This appears to be the first report of an anti-cancer effect of CySSPe.

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